103-89-9

Usage

Uses

Used in Pharmaceutical Industry:
p-Acetotoluidide is used as a precursor in penicillin synthesis and other pharmaceuticals, including painkillers and intermediates. It is also used as an intermediate for the synthesis of rubber accelerators, dyes, and dye intermediates.
Used in Chemical Industry:
p-Acetotoluidide is used as an inhibitor of peroxides and a stabilizer for cellulose ester varnishes.
Used in Synthesis:
p-Acetotoluidide is used as an intermediate in the synthesis of stable crystalline phosphorus ylides.

Synthesis Reference(s)

Journal of the American Chemical Society, 77, p. 5092, 1955 DOI: 10.1021/ja01624a042Organic Syntheses, Coll. Vol. 1, p. 111, 1941Synthesis, p. 118, 1977

Air & Water Reactions

Water insoluble.

Reactivity Profile

4'-Methylacetanilide is an amide. Flammable gases are formed by the reaction of organic amides with strong reducing agents. Amides are very weak bases (weaker than water). Imides are less basic yet and in fact react with strong bases to form salts. That is, they can react as acids. Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).

Health Hazard

ACUTE/CHRONIC HAZARDS: When heated to decomposition 4'-Methylacetanilide emits toxic fumes.

Health Hazard

Exposures to p-acetotoluidide through ingestion or inhalation cause potential health effects. The symptoms of toxicity include, but are not limited to, irritation to the eyes and redness of the skin, wheezing, cough, shortness of breath, or burning in the mouth, throat, or chest, and respiratory tract irritation.

Safety Profile

Moderately toxic by ingestion. See also ACETANILIDE. Combustible. When heated to decomposition it emits toxic fumes of NO,. To fight fire, use water, foam, CO2, dry chemical

storage

p-Acetanilide should be kept stored in a cool, dry place with the container closed when not in use

Purification Methods

Crystallise it from aqueous EtOH. [Beilstein 12 H 920, 12 I 420, 12 II 501, 12 III 2051, 12 IV 1902.]

Precautions

During handling and use of p-aetotoluidide, proper personal protective equipment should be worn. Avoid contact with the eyes, skin, and clothing. Avoid ingestion and inhalation. On accidental exposure at the workplace, workers should immediately fl ush the eyes and exposed part of the body with plenty of water. Workers should avoid using the contaminated clothing and shoes.

Upstream product

• 625-77-4 N-acetylacetamide 
• 540-23-8 p-toluidine hydrochloride 
• 99-99-0 1-methyl-4-nitrobenzene 
• 108-24-7 acetic anhydride 
• 106-49-0 p-toluidine 
• 71-43-2 benzene 
• 10532-64-6 N-(4-methylphenyl)cyanamide 
• 621-01-2 N,N'-Bis(p-tolyl)thiourea 
• 60-35-5 acetamide 
• 64-19-7 acetic acid 
• 86012-53-5 2,4-bis(p-methylanilino)-1,3-bis(p-methylphenyl)-1,3,2,4-diazadiphosphetidine 
• 108-88-3 toluene 
• 107-06-2 1,2-dichloro-ethane 
• 876479-63-9 acetic acid-(N'-phenyl-N-p-tolyl-hydrazide) 

Downstream Products

• 24303-02-4 N-(4-methylphenyl)-3-pyridinecarboxamide 
• 18931-78-7 N-(2-chloro-4-methylphenyl)acetamide 
• 5132-17-2 N,N'-di(p-tolyl)acetamidine 
• 613-48-9 N,N-diethyl-p-toluidine 
• 63913-32-6 (5-acetylamino-2-methyl-phenyl)-chloro-acetic acid 
• 63913-33-7 acetic acid-[4-methyl-3-(1,2,2,2-tetrachloro-ethyl)-anilide] 
• 7472-91-5 4-methyl-diacetanilide 
• 100191-84-2 N-(prop-2-yn-1-yl)-N-(p-tolyl)acetamide 
• 109532-28-7 2-(Acetylamino)-α-chlor-5-methylacetophenon 
• 99-99-0 1-methyl-4-nitrobenzene 
• 826-77-7 4,6-dimethylquinoline 
• 95460-01-8 N-Acetyldiphenylacetotoluidide 
• 620-84-8 4-methyldiphenylamine 
• 145473-87-6 1-(4-methylphenyl)-1-phenyl-2-propanone 

Relevant academic research and scientific papers

Solvent free Beckmann rearrangement of ketoximes by anhydrous ferric chloride

Beckmann rearrangement of ketoximes is achieved efficiently by anhydrous FeCl3 in the absence of solvent. Unsymmetrical oximes are selectively produced one of the two possible products in good yields. Similar reactions are not occurred in the presence of solvent.

Silica–ferric chloride (SiO2–FeCl3) catalyzed selective synthesis of 2-substituted benzimidazole through Csp2Csp3bond cleavage of β-ketoester/amide

Silica–ferric chloride (SiO2–FeCl3) supported reagent was successfully utilized as recyclable catalyst for the general and highly efficient synthesis of 2-substituted benzimidazole by the condensation of 1,2-diamino benzene and β-ketoester/amide followed by original Csp2Csp3bond cleavage. Evidences in favor of C[sbnd]C (α–β) bond cleavage of β-ketoesters/amides are established.

Study of 4-acetylaminotoluene ozonation in acetic acid

The reaction of 4-aminotoluene with ozone in acetic acid was studied. It was found that the reaction proceeds at a high rate, giving predominantly tars. The product composition changes after acylation of the amino group: aliphatic peroxides prevailed among the oxidation products and 4-acetylaminobenzoic acid was identified (16%) as well. It was shown that the presence of a catalyst (cobalt(II) acetate) had no substantial effect on the oxidation selectivity for the methyl group (32%) and only the addition of potassium bromide increased the activity of the catalyst; the yield of 4-acetylaminobenzoic acid reached 70%. The mechanism of oxidation in the presence of a cobalt-bromide catalyst explaining the obtained results was discussed.

Antimicrobial and antileishmanial studies of novel (2E)-3-(2-chloro-6- methyl/methoxyquinolin-3-yl)-1-(aryl)prop-2-en-1-ones

Thirty eight heterocyclic chalcones were synthesized by condensing formylquinolines with diverse methyl arylketones. The target compounds were characterized by spectroscopic techniques (NMR, IR, MS) and elemental analysis. The X-ray crystallographic study of (2E)-3-(2-chloro-6-methylquinolin-3-yl)-1- (2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one (1p) was also performed for the structure confirmation. The title compounds were screened for anti-microbial and antileishmanial activities. The compounds 1c - e, 1g, 1j - m, 1p, 1r - s, 2g, 2j - p, and 2r - s were found potentially active antileishmanial agents, while 1f - i, 1l, 1o - p, 2f - i, 2l, and 2o - p showed remarkable antibacterial activity. Only compounds 1g and 2g - h exhibited significant antifungal activity.

Novel tetrazoloquinoline-thiazolidinone conjugates as possible antitubercular agents: Synthesis and molecular docking

A novel approach for the synthesis of a new 4-thiazolidinone scaffold was developed by a one-pot three-component cyclocondensation of various tetrazolo quinoline aldehydes 1a-f, acid hydrazide 2a-c, and thioglycolic acid 3 in the presence of [DBUH][OAc] as a catalyst in high yields. All the conjugates were screened for their antimycobacterial activity against MTB H37Ra and M. bovis BCG strains, with the MIC values ranging from 0.99-13.55 μmol mL-1 and 0.14-20.11 μmol mL-1, respectively. The 4-thiazolidinone-incorporated tetrazoloquinoline derivatives 4a, 4d, 4g, 4j, 4m, and 4p were highly potent against MTB H37Ra and M. bovis BCG strains. The most active compounds were also evaluated for their cytotoxicity against MCF-7, A549, and HCT 116 cell lines and were found to be non-cytotoxic. Further, molecular docking studies into the active site of the InhA enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping us to understand the ligand-protein binding interaction and establish a structural basis for the inhibition of mycobacterium tuberculosis. The results suggest that the tetrazoloquinoline-thiazolidinone conjugates 4a, 4d, 4g, 4j, 4m, and 4p are promising antitubercular agents.

Anti-HIV-1 screening of (2E)-3-(2-chloro-6-methyl/methoxyquinolin-3-yl)-1- (aryl)prop-2-en-1-ones

Biological studies of two series of 38 quinolinyl chalcones (4a-s and 5a-s) were investigated for their in vitro anti-HIV-1 and cytotoxic activities. Out of 38 compounds, seventeen compounds were observed as good anti-HIV-1 agents with EC50 values less than 20 μM. Compounds 4a, 4l, 4o, 5e, 5h, 5l, 5o, and 5r displayed potent anti-HIV-1 activity with EC50 values less than 5 μM. Among these, compound 5h emerged as the best anti-HIV-1 agent (EC50 = 1.1 μM). Compounds 4d, 4n, 4q, 4r, 4s, 5n, and 5r showed no toxicity in human lymphocytes. Bioassay results show that the type(s) and position(s) of the substituents seem to be critical for their cytotoxic and anti-HIV-1 activities. These results could be useful in the invention of new anti-HIV agents through structural modification.

Discovery and molecular docking of quinolyl-thienyl chalcones as anti-angiogenic agents targeting VEGFR-2 tyrosine kinase

Vascular endothelial growth factor Receptor-2 (VEGFR-2) kinase inhibition is one of the well established strategies to promptly tackle tumor growth by suppression of angiogenesis. In the current study, structure-based virtual screening methodology of a series of quinolyl-thienyl chalcones indicated their strong potential as VEGFR-2 kinase inhibitors. In vitro VEGFR-2 kinase inhibitory activity was found to be significant (compound 19, IC50: 73.41 nM). All compounds showed significant inhibition of human umbilical vein endothelial cells (HUVEC) proliferation (compound 19, IC50: 21.78 nM). Molecular interactions of the compounds were studied using molecular docking studies.

Synthesis and Bioactivity of Quinoline-3-carboxamide Derivatives

Twelve novel substituted 2-chloroquinoline-3-carboxamide derivatives were prepared from acetanilides using the Vilsmeier–Haack reaction, producing 2-chloro-3-carbaldehyde quinolines, followed by oxidation of the 3-carbaldehyde to the carboxylic acid and coupling this group with various anilines. The structures of the synthesized compounds were confirmed by NMR, mass spectrometry, and single crystal X-ray diffraction. The chemical shifts of H-5 and H-8 were shown to be influenced by the substituent at C-6. The substituent at C-6 was also seen to affect the chemical shift of C-5, C-7, and C-8, with C-5 and C-7 being more shielded in 5j (F substituted) in comparison with 5g (Cl substituted) and 5d (CH3 substituted). The compounds showed weak activity in the mM range against Gram-positive and Gram-negative bacteria of which 5b, 5d, and 5f showed the best activity with minimum bactericidal concentration values for 5b being 3.79?mM against methicillin-resistant Staphylococcus aureus and 5d and 5f having minimum bactericidal concentration values of 3.77 and 1.79?mM against S.?aureus ATCC 25923, respectively.

Paracetamol and other acetanilide analogs as inter-molecular hydrogen bonding assisted diamagnetic CEST MRI contrast agents

Paracetamol and a few other acetanilide derivatives are reported as a special class of diamagnetic Chemical Exchange Saturation Transfer (diaCEST) MRI contrast agents, that exhibit contrast only when the molecules form inter-molecular hydrogen bonding mediated molecular chains or sheets. Without the protection of the hydrogen bonding their contrast producing labile proton exchanges too quickly with the solvent to produce any appreciable contrast. Through a number of variable temperature experiments we demonstrate that under the conditions when the hydrogen bond network breaks and the high exchange returns back, the contrast drops quickly. The well-known analgesic drug paracetamol shows 12% contrast at a concentration of 15 mM at physiological conditions. With the proven safety track-record for human consumption and appreciable physiological contrast, paracetamol shows promise as a diaCEST agent forin vivostudies.

Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation

In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 μg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.